Both HIV infection and depression are independent risk factors for incident heart failure, and living with both HIV and depression multiplies the risk, according to an analysis of data from the Veterans Aging Cohort Study presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston.

"These findings highlight the importance of identifying depression among those with HIV," said Jessica White, a doctoral student at the University of Pittsburgh Graduate School of Public Health who presented on Tuesday.

HIV infection and depression both have previously been associated with an increased risk of heart failure. There is a high prevalence of clinical depression among adults living with HIV. Could this partly account for the increased risk of heart failure among people with HIV, or could depression increase the risk?

As part of her doctoral dissertation, White decided to explore the association between HIV, depression, and heart failure by analyzing data from the Veteran’s Aging Cohort Study, which includes longitudinal data from HIV positive veterans matched to HIV negative veterans by age, sex, race/ethnicity, and region.

The analysis included data on 81,427 veterans without pre-existing cardiovascular disease, 33% of them HIV positive. Most were men. They were followed from their first clinical encounter on or after April 1, 2003, until a heart failure event, death, or their last follow-up visit through December 31, 2009. Medical records were reviewed to see whether the veterans were suffering from a major depressive disorder (MDD) at baseline, which clinicians would have noted using ICD-9 codes.

Participants were stratified into 4 groups using baseline diagnoses of MDD and HIV status: HIV negative without depression (referent), HIV negative with depression; HIV positive without depression; and HIV positive with depression.

At baseline, other risk factors that might be associated with heart disease in this group were consistent with what has been reported in previous studies. For instance, diabetes and obesity were less prevalent among people living with HIV than those without, and smoking and substance use were more common in both people with MDD and HIV.

Results

Over a median of 5.9 years of follow-up, there were 2666 heart failure events, of which 38% occurred in HIV positive veterans.

Among the 45,728 veterans without either HIV or MDD, there were 1339 cases of heart failure over the course of the study, which represented a rate of 60.4 per 10,000 person-years; this group serves as the reference group, with a hazard ratio (HR) of 1.0.

Among the 8,791 depressed but HIV negative veterans, there were 319 heart failure events, for a rate of 68.7 per 10,000 person-years, with a HR of 1.19.

There were 774 heart failures among the 21,850 HIV positive veterans without depression, for a rate of 75.6 per 10,000 person-years, with a HR of 1.28.

There were 234 heart failures among the 5058 veterans with HIV who also had MDD, a rate of 93.2 per 10,000 person-years, with a HR of 1.68.

Compared to veterans without either condition, those with only MDD or with only HIV had significantly higher rates of heart failure.

Veterans living with both HIV and depression had the highest risk of heart disease -- more than 68% higher than those without either condition.

After adjusting for strong risk factors such as age, hypertension, and kidney disease, MDD remained a significant risk factor for heart failure in HIV positive veterans after adjusting for covariates and baseline antiretroviral therapy (ART) regimen, CD4 count, and viral load (HR 1.30).

This was also the case in an analysis adjusting for recent (within 6 months of a heart failure event) ART regimen, recent CD4 count, and recent viral load (HR 1.27).

"From this study we concluded that both depression and HIV are associated with increased risk of heart failure, and those with both HIV and MDD have the highest rates and risk of heart failure," said White.

The explanation for why people living with HIV and depression are at a much greater risk of heart failure, however, was a topic of heated debate following White’s presentation. Again, these findings were independent of other factors that are commonly associated with heart disease.

One possibility is that at least some of increased risk might be due to greater ascertainment of heart failure in people living with HIV, for example, because they tend to utilize healthcare more than the rest of the population. Conversely, the same argument could be used to suggest that heart failure is more common among depressed people, because they are not seeking medical care enough.

Could depression itself be causing heart failure? Could factors related to HIV infection -- such as chronic inflammation -- contribute to both the depression and the increased risk of cardiovascular disease? What about the use of antidepressants?

"As far as the anti-depressants go, we did not include that in this analysis," said White. "We do recognize the importance and how those may have some cardiovascular implications, but that is yet to be done."

White also plans to look at the severity of depressive symptoms as well as biomarker data -- such as inflammatory biomarkers -- in further analyses.